Nuclear alignment in myotubes requires centrosome proteins recruited by nesprin-1

Abstract

Myotubes are syncytial cells, generated by fusion of myoblasts. Among the numerous nuclei in myotubes of skeletal muscle fibres, the majority are equidistantly positioned at the periphery, except for clusters of multiple nuclei underneath the motor endplate. The correct positioning of nuclei is thought to be important for muscle function and requires nesprin-1, a protein of the nuclear envelope. Consistently, mice lacking functional nesprin-1 show defective nuclear positioning and mimic aspects of Emery-Dreifuss muscular dystrophy. In this study, we perform siRNA experiments in C2C12 myoblasts undergoing differentiation, demonstrating that the positioning of nuclei requires PCM-1, a protein of the centrosome that relocalizes to the nuclear envelope at the onset of differentiation, dependent on the presence of nesprin-1. PCM-1 itself is required for recruiting proteins of the dynein/dynactin complex and of kinesin motor complexes. This suggests that microtubule motors that are attached to the nuclear envelope support the movement of nuclei along microtubules, to ensure correct positioning in the myotube.